The scientists, Christopher Rathnam and colleagues, say they have designed a way of controlling the formation of 3D spheroids made from stem cells, while enhancing the spheroids’ ability to differentiate into functional neurons.
The technology led to an increase in stem cell survival and differentiation – two challenges with existing stem cell therapy systems – in a mouse model of spinal cord injury, noted the team in a paper published in Science Advances
“We believe that our technology platform is an ideal candidate for improving many other types of cell therapies that require high cell survival and effective control of cell fate, making it useful not only for treating [spinal cord injuries] but also for various other diseases and disorders,” said the authors.
Stem cell therapy challenges
Although stem cell therapy holds enormous potential for treating debilitating injuries and diseases of the CNS, the team outlined how low survival and inefficient differentiation have restricted its clinical applications.
Recently, 3D cell culture methods, such as stem cell–based spheroids and organoids, have demonstrated advantages by incorporating tissue-mimetic 3D cell-cell interactions, said the experts.
However, a lack of drug and nutrient diffusion, insufficient cell-matrix interactions, and tedious fabrication procedures have compromised their therapeutic effects in vivo, they added.
To address these issues, the Rathnam led team developed a method in which biodegradable manganese dioxide nanosheets guide the rapid assembly of neural stem cells, derived from human induced pluripotent stem cells (iPSCs), into 3D spheroids.
The technique also enables controlled drug release inside the core of the spheroids, which could help to improve cell survival and differentiation, they said.
To evaluate the efficacy of the structures, which they termed synthetic matrix-assisted and rapidly templated (SMART) spheroids, the researchers implanted them at injury sites in a mouse model of spinal cord injury.
As controls, they injected cell suspensions and conventional neurospheres, formed without the use of their novel nanosheets, at the spinal cord injury sites, with the same total number of cells per animal and at the same concentrations.
They found significantly higher cell survival and improved neuronal differentiation efficiency for the SMART neurospheres compared with the controls both 7 days and 1 month after injection.